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The Botanical Drug PBI-05204, a Supercritical CO2 Extract of Nerium Oleander, Is Synergistic With Radiotherapy in
Alessandro Colapietro1, Peiying Yang2, Alessandra Rossetti1
1Laboratory of Radiobiology, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
Abstract:
Glioblastoma multiforme (GBM) is the most common as well as one of the most malignant types of brain cancer. Despite progress in development of novel therapies for the treatment of GBM, it remains largely incurable with a poor prognosis and a very low life expectancy. Recent studies have shown that oleandrin, a unique cardiac glycoside from Nerium oleander, as well as a defined extract (PBI-05204) that contains this molecule, inhibit growth of human glioblastoma, and modulate glioblastoma patient-derived stem cell-renewal properties. Here we demonstrate that PBI-05204 treatment leads to an increase in vitro in the sensitivity of GBM cells to radiation in which the main mechanisms are the transition from autophagy to apoptosis, enhanced DNA damage and reduced DNA repair after radiotherapy (RT) administration. The combination of PBI-05204 with RT was associated with reduced tumor progression evidenced by both subcutaneous as well as orthotopic implanted GBM tumors. Collectively, these results reveal that PBI-05204 enhances antitumor activity of RT in preclinical/murine models of human GBM. Given the fact that PBI-05204 has already been examined in Phase I and II clinical trials for cancer patients, its efficacy when combined with standard-of-care radiotherapy regimens in GBM should be explored.
Insights
Oleandrin extract PBI-05204 enhances radiation therapy effectiveness against glioblastoma. This novel approach increases cancer cell death and reduces tumor growth in preclinical models, suggesting potential for clinical trials.
Area of Science:
- Oncology
- Pharmacology
- Cancer Biology
Background:
- Glioblastoma multiforme (GBM) is an aggressive brain cancer with poor prognosis.
- Current treatments for GBM offer limited efficacy.
- Oleandrin, a cardiac glycoside from *Nerium oleander*, and its extract PBI-05204 show potential in inhibiting glioblastoma growth.
Purpose of the Study:
- To investigate the effect of PBI-05204 on glioblastoma cell sensitivity to radiation.
- To elucidate the mechanisms by which PBI-05204 enhances radiotherapy efficacy.
- To evaluate the combination of PBI-05204 and radiotherapy in preclinical GBM models.
Main Methods:
- In vitro assessment of PBI-05204's effect on GBM cell radiosensitivity.
- Analysis of cellular mechanisms including autophagy, apoptosis, DNA damage, and repair.
- Evaluation of tumor progression in subcutaneous and orthotopic GBM xenograft models.
Main Results:
- PBI-05204 increased GBM cell sensitivity to radiation in vitro.
- Mechanisms involved a shift from autophagy to apoptosis, increased DNA damage, and reduced DNA repair post-radiotherapy.
- Combination therapy with PBI-05204 and radiotherapy reduced tumor progression in preclinical models.
Conclusions:
- PBI-05204 enhances the antitumor activity of radiotherapy in glioblastoma.
- The findings support further investigation of PBI-05204 combined with radiotherapy for GBM treatment.
- PBI-05204's prior clinical trial examination warrants exploration in standard-of-care radiotherapy regimens for GBM.
